The spindle assembly checkpoint is satisfied in the absence of interkinetochore tension during mitosis with unreplicated genomes.

The spindle assembly checkpoint is satisfied in the absence of interkinetochore tension during mitosis with unreplicated genomes.
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DOI:
10.1083/jcb.200801038
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发表时间:
2008-10-06
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Khodjakov A
Khodjakov A
中科院分区:
其他
文献类型:
--
作者:
O'Connell CB;Loncarek J;Hergert P;Kourtidis A;Conklin DS;Khodjakov A

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纺锤体组装检查点(SAC)的存在提高了染色体分离的准确性。SAC被认为监测两个不同的事件:着丝粒与微管的连接,以及姐妹着丝粒之间的着丝粒的拉伸,只有当染色体正确地双向取向时才会出现。我们研究了人类细胞进行有丝分裂与未复制的基因组(MUG)。这些细胞中的动粒不成对,这意味着着丝粒不能被拉伸;然而,细胞通过有丝分裂进行。SAC在MUG期间存在,因为细胞响应于诺考达唑、紫杉醇或monastrol治疗而停滞。Mad2被募集到未连接的MUG动粒,并在它们连接时释放。相反,BubR1仍然附着在着丝粒上,并表现出与MUG纺锤体无法建立正常水平的着丝粒张力相一致的磷酸化水平。因此,即使在不存在动粒间张力的情况下,动粒与微管的附着也足以满足SAC。
The accuracy of chromosome segregation is enhanced by the spindle assembly checkpoint (SAC). The SAC is thought to monitor two distinct events: attachment of kinetochores to microtubules and the stretch of the centromere between the sister kinetochores that arises only when the chromosome becomes properly bioriented. We examined human cells undergoing mitosis with unreplicated genomes (MUG). Kinetochores in these cells are not paired, which implies that the centromere cannot be stretched; however, cells progress through mitosis. A SAC is present during MUG as cells arrest in response to nocodazole, taxol, or monastrol treatments. Mad2 is recruited to unattached MUG kinetochores and released upon their attachment. In contrast, BubR1 remains on attached kinetochores and exhibits a level of phosphorylation consistent with the inability of MUG spindles to establish normal levels of centromere tension. Thus, kinetochore attachment to microtubules is sufficient to satisfy the SAC even in the absence of interkinetochore tension.